The long-term goals are to gain a better understanding of the central regulation of cardiovascular function. During the previous periods, cardiovascular reflex mechanisms were studied in normotensive and hypertensive animals. This was followed by the identification of he pressor and depressor areas in the ventrolateral medulla. Our current research interests are focussed on the functional relationship between different medullary cardiovascular areas, their interaction with intermediolateral column of the thoraco-lumbar spinal cord (IML) and identification of putative neurotransmitters in the pathways interconnecting these cardiovascular regulatory mechanisms. The following hypotheses form the basis of this proposal: (1) Activation of different visceral afferents results in the release of specific transmitters in the nucleus tractus solitarius. Separate populations of secondary neurons and their target structures are activated. (2) The pressor area in the ventrolateral medulla (VLPA) constitutes the final relay in the medulla through which cardiovascular responses are mediated. (3) The projection from the VLPA to the IML release excitatory transmitters such as acetylcholine, glutamate or substance P at their terminals. (4) Different excitatory transmitters may be released in the regions of the IML controlling cardiac and vasomotor functions. To test these hypotheses, the following approaches will be used: (1) MEdullary pathways activated by different excitatory and inhibitory transmitters will be identified by microinjection technique. (2) The role of these pathways in various reflexes will be studied. (3) Various putative transmitters will be applied microiontophoretically on sympathetic preganglionic neurons in the IML and the responses will be analyzed. These studies will provide a better understanding of cardiovascular regulation under normal conditions. Eventually these results may open new avenues for treating cardiovascular diseases such as hypertension.